title: New α-lipoic acid derivative, DHL-HisZn, ameliorates renal ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) occurs frequently in a variety of clinical settings, such as renal transplantation. In addition, I/R is a major cause of acute kidney injury (AKI). A recent study has reported that reactive oxygen species (ROS) are important mediators of AKI, suggesting that reducing ROS generation may prevent renal injury. The present study evaluated the ability of DHL-HisZn, a new α-lipoic acid derivative, to inhibit ROS generation and prevent renal I/R injury in rats.
  
  
  METHODS
  Rats received an intravenous infusion of DHL-HisZn or saline, and then underwent experimentally induced renal I/R injury or sham treatment. Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion. To evaluate the renal protective effects of DHL-HisZn, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and malondialdehyde (MDA), a biomarker of oxidative stress, was evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with DHL-HisZn to assess its antioxidant effects in vitro.
  
  
  RESULTS
  DHL-HisZn treatment attenuated I/R-induced histologic alterations, reduced serum levels of serum BUN and Cre, and decreased MDA levels in the kidneys of rats with renal I/R injury. Furthermore, DHL-HisZn decreased ROS levels in AMA-stimulated RAW264.7 cells.
  
  
  CONCLUSIONS
  Our in vitro and in vivo findings suggest that DHL-HisZn may have therapeutic potential against various human I/R conditions.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University, Faculty of Medicine, Oita, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Jyunya
authors.initials: J
authors.lastname: Kusaka
authors.forename: Koji
authors.initials: K
authors.lastname: Goto
authors.forename: Tetyuya
authors.initials: T
authors.lastname: Uchino
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shingu
authors.forename: Shinya
authors.initials: S
authors.lastname: Kai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D017382:Reactive Oxygen Species; C572452:zinc histidine dithiooctanamide; D006639:Histidine; D008315:Malondialdehyde; D008063:Thioctic Acid